Department of Chemistry, Portland State University, Portland, Oregon 97207, USA.
RNA. 2019 Apr;25(4):453-464. doi: 10.1261/rna.068908.118. Epub 2019 Jan 22.
There are several plausible abiotic synthetic routes from prebiotic chemical materials to ribonucleotides and even short RNA oligomers. However, for refinement of the RNA World hypothesis to help explain the origins of life on the Earth, there needs to be a manner by which such oligomers can increase their length and expand their sequence diversity. Oligomers longer than at least 10-20 nucleotides would be needed for raw material for subsequent natural selection. Here, we explore spontaneous RNA-RNA recombination as a facile means by which such length and diversity enhancement could have been realized. Motivated by the discovery that RNA oligomers stored for long periods of time in the freezer expand their lengths, we systematically investigated RNA-RNA recombination processes. In addition to one known mechanism, we discovered at least three new mechanisms. In these, one RNA oligomer acts as a splint to catalyze the hybridization of two other oligomers and facilitates the attack of a 5'-OH, a 3'-OH, or a 2'-OH nucleophile of one oligomer onto a target atom of another. This leads to the displacement of one RNA fragment and the production of new recombinant oligomers. We show that this process can explain the spontaneous emergence of sequence complexity, both in vitro and in silico.
有几种合理的非生物合成途径可以将前生物化学物质转化为核苷酸，甚至是短的 RNA 寡聚物。然而，为了完善 RNA 世界假说，以帮助解释地球上生命的起源，需要有一种方法可以使这些寡聚体增加其长度并扩展其序列多样性。至少需要 10-20 个核苷酸长的寡聚体作为后续自然选择的原材料。在这里，我们探讨了自发的 RNA-RNA 重组作为实现这种长度和多样性增强的简便方法。受发现 RNA 寡聚体在冰箱中长时间储存会增加其长度的启发，我们系统地研究了 RNA-RNA 重组过程。除了一种已知的机制外，我们还发现了至少三种新的机制。在这些机制中，一个 RNA 寡聚体充当衔接物，催化两个其他寡聚体的杂交，并促进一个寡聚体的 5'-OH、3'-OH 或 2'-OH 亲核试剂攻击另一个寡聚体的靶原子。这导致一个 RNA 片段的置换和新重组寡聚体的产生。我们表明，这个过程可以解释体外和计算机模拟中序列复杂性的自发出现。
